A critical assessment of insulin sensitivity in women with and without breast cancer. Breast cancer continues to be a leading cause of death in women in the United States. It accounts for 18% of all female cancer deaths and approximately 46,000 women will die of breast cancer each year. Breast cancer risk has been associated with Western life-style, but it is difficult to identify what aspects of life impose this large risk for disease If these factors could be identified, preventative measures could be taken to reduce the risk level. The focus of this study is the exploration of a novel risk factor for breast cancer, namely insulin resistance and the presence of an excess amount of insulin in the blood (hyperinsulinemia). It has become clear that Western life-style is associated with an increase waist-to-hip ratio, also known as the apple shape, as opposed to the pear shape. Studies have shown that apple shaped women, despite normal glucose tolerance, are insulin resistant. The apple shape and obesity are recognized risks for the development of breast cancer and it seems likely that hyperinsulinemic insulin resistance represents the common feature responsible for this increased risk. Hyperinsulinemia associated with insulin resistance has been shown to effect multiple aspects of human sex steroid metabolism as well as rapid cellular growth. Thus, several mechanisms exist by which hyperinsulinemic insulin resistance could promote the development of breast cancer. The above observations suggest that hyperinsulinemic insulin resistance may represent both an early marker for disease predisposition as well as a reversible risk factor for breast cancer. Subjects from the Massey Cancer Center at MCV and from the mammography center at MCV will be invited to participate in the study. Medical histories will be taken, and social histories (smoking, exercise, alcohol intake) will be evaluated. Women with known diabetes mellitis will be excluded. There will be two groups, one of women with breast cancer and the other of women without breast cancer. 200 women in the study will come to the General Clinical Research Center after an overnight fast. Height, weight, waist-to-hip ratio, and percent body fat will be recorded. Fasting blood samples will be drawn for determination of basal serum insulin, glucose, estrogen, androgen, and sex hormone binding globulin levels. An insulin tolerance test will be given to assess insulin sensitivity. Four groups of variables will be identified: insulin sensitivity, biochemical factors, heredity factors, and lifestyle factors. Analysis of these groups will help identify risk factors.